The presence of circulating immune complexes in Hodgkin's disease provides evidence for the possible existence of a Hodgkin-related antigen (HRA) with an in vivo immune response by the patient producing anti-HRA antibody. It is planned to take the patient's lymphocytes, sensitized in vivo versus the HRA antigen, and perform fusion experiments with both murine and human neoplastic B-cell lines to produce hybridomas capable of secreting the anti-HRA antibody. Preliminary studies have already established the feasibility of all stages of this work up to and including the production by hybridoma clones of human immunoglobulin with reactivity versus Hodgkin's disease tissue (Reed-Sternberg cells). Additional screening and cloning studies are progressing to further assess the specificity of antibodies obtained. In this work we intend to extend these preliminary studies to perform human lymphocyte fusions on 6 to 12 patients with Hodgkin's disease, to assess the specificity of the various human immunoglobulins obtained utilizing tissue sections and cytocentrifuge preparations, to prepare sufficient antibody for use in purification of any Hodgkin-related antigens, and finally to employ purified anti-HRA antibody and HRA antigen for immunohistologic and serologic studies relating to the diagnosis and pathogenesis of Hodgkin's disease. At this point, we anticipate that it may also be possible to plan detailed studies using anti-HRA and/or HRA for rad-localization studies and Phase I therapeutic approaches (reaction with human anti-HRA or use of HRA as a "vaccine"); we believe such studies could be very exciting. They cannot, however, be formulated without first successfully completing this current work. (2)